Normal human aging is typically characterized by a decline in several domains of cognitive function. However, not all individuals evidence such decline with age. The neurobiological that underlies the differences in the degree of unsuccessful aging remains unclear. Several possibilities have been advanced ranging from widespread cortical loss and the presence and extent of neuritic plaques have now been eliminated as primary factors underlying age-related cognitive decline. Rather, our findings have pointed to white matter degradation, alterations in layer I of the cerebral cortex, and inflammation as possible key factors. Accordingly, in this next stage of our program, we will assess cognition in a group of 96 rhesus monkeys spanning the adult age range, and in particular those of late middle age. We will then relate the behavioral outcome variables from the individual tasks to a set of regional (temporal lobe will then relate to the behavioral outcome variables from the individual tasks to a set of regional (temporal lobe limbic system, area 46 and visual cortex) morphologic, immunocytochemical, physiologic, neuroimaging and biochemical outcome variables measured in the other three projects. One additional variable, based on a composite score derived from the behavioral test battery will be used to assess global cognitive changes with global outcome measures from the other three projects. This latter approach has yielded findings of a significant relationship between cognitive decline and loss of white matter and myelin degeneration in our aged monkeys and points to the possibility that aging in the brain may have widespread and generalized effects. The three specific aims of this project are as follows: Specific Aim 1 is to assess the performance of aged and young adult monkeys on tasks of visual recognition memory, spatial, and memory, spatial memory, and executive system function that are known to be sensitive to aging in both monkey and human populations. Specific Aim 2 is to characterize, for the first time, cognitive function in a group of late middle aged monkeys. Specific Aim 3 (Collaborative with Project 4) is to evaluate visual function by assessment of degraded figures in aged and young adult monkeys.